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  • Title: Enhancement of thrombocyte aggregation and thromboxane B2 synthesis by diethylstilbestrol.
    Author: Subbiah MT, Gallon L, Yunker R.
    Journal: Pharmacology; 1980; 21(6):396-9. PubMed ID: 7220591.
    Abstract:
    Effect of diethylstilbestrol administration on thrombocyte aggregation and thromboxane B2 synthesis was investigated in atherosclerosis-susceptible pigeons. Platelet aggregatory response to arachidonic acid and synthesis of thromboxane B2 from 14C-arachidonic acid was enhanced in thrombocytes derived from diethylstilbestrol-treated pigeons. Platelet total phospholipid concentration was increased in pigeons with diethylstilbestrol treatment. Enhanced thromboxane synthesis might be responsible for increased platelet aggregation, which in turn might contribute to the severe atherosclerosis noted following diethylstilbestrol treatment in several avian species. This study examines the effects of diethylstilbestrol administration on thrombocyte aggregation and thromboxane B2 synthesis. Diethylstilbestrol (10 mg/kg in sesame oil) was injected intramuscularly each week for 2 weeks in female white Carneau pigeons who were susceptible to atherosclerosis. Blood samples were drawn from the heart, titrated and centrifuged. Washed platelets were isolated and suspended for use in experiments involving incubation with C14-arachidonic acid. Gas-liquid chromatography was used to determine fatty acid composition of platelet phospholipids. The estrogen-treated thrombocytes exhibited more aggregatory response to arachidonic acid than those of control birds. To determine whether synthesis of proaggregatory thromboxane A2 (measured as thromboxane B2) by platelets is affected, conversion of C14-arachidonic acid into various prostaglandins by platelets was measured. Synthesis of thromboxane B2 in DES-treated thrombocytes was significantly higher (p0.05) than in normal thrombocytes. No significant difference was found in the formation of other prostaglandins. Total phospholipid level (mcg/mg protein) was higher in DES-treated platelets (18.2 +or- 3.5 in control thrombocytes vs. 26.7 +or- 3.1 in DES-treated thrombocytes). The study shows that diethylstilbestrol stimulates thrombocyte aggregation, confirming the report of increased platelet aggregation in women on oral contraceptives.
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